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使用 MITO-Porter 将邦克酸递送至线粒体可防止人宫颈癌细胞系 HeLa 细胞凋亡的诱导。

Mitochondrial delivery of bongkrekic acid using a MITO-Porter prevents the induction of apoptosis in human HeLa cells.

机构信息

Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.

出版信息

J Pharm Sci. 2013 Mar;102(3):1008-15. doi: 10.1002/jps.23442. Epub 2013 Jan 11.

Abstract

The fact that mitochondrial dysfunction has been implicated in a variety of human diseases suggests that they would be expected as a target organelle for these diseases. Bongkrekic acid (BKA) is a chemical that functions as a ligand of the adenine nucleotide translocator and is known to potently inhibit the mitochondrial permeability transition that is associated with apoptosis. Thus, delivering it to mitochondria would be an innovative therapy for the treatment of mitochondrial diseases that are largely associated with apoptosis. Here, we report on the use of a MITO-Porter, an innovative nanocarrier for mitochondrial delivery via mitochondrial membrane fusion, for delivering BKA to mitochondria. We first constructed a BKA-MITO-Porter, in which BKA is contained in lipid envelopes of a MITO-Porter. We then confirmed that the BKA-MITO-Porter was efficiently internalized into cells and is delivered to mitochondria, similar to a conventional MITO-Porter. Moreover, we evaluated the antiapoptosis effect of the BKA-MITO-Porter in HeLa cells by measuring caspase 3/7 activity. The findings confirmed that the BKA-MITO-Porter showed a strong antiapoptosis effect compared with naked BKA. The results reported here demonstrate its potential for the use in therapies aimed at mitochondrial diseases, as a mitochondrial medicine candidate.

摘要

线粒体功能障碍与多种人类疾病有关,这表明它们可能成为这些疾病的靶向细胞器。Bongkrekic 酸(BKA)是一种作为腺嘌呤核苷酸转位酶配体起作用的化学物质,已知它能强烈抑制与细胞凋亡相关的线粒体通透性转换。因此,将其递送到线粒体将是治疗与细胞凋亡密切相关的线粒体疾病的一种创新疗法。在这里,我们报告了一种 MITO-Porter 的使用情况,MITO-Porter 是一种通过线粒体膜融合进行线粒体递药的创新纳米载体,用于将 BKA 递送到线粒体。我们首先构建了 BKA-MITO-Porter,其中 BKA 包含在 MITO-Porter 的脂质包膜中。然后,我们证实 BKA-MITO-Porter 能够有效地被细胞内化并递送到线粒体,类似于传统的 MITO-Porter。此外,我们通过测量半胱天冬酶 3/7 活性来评估 BKA-MITO-Porter 在 HeLa 细胞中的抗凋亡作用。研究结果证实,与裸 BKA 相比,BKA-MITO-Porter 表现出更强的抗凋亡作用。本研究结果表明,它可能作为一种线粒体药物候选物,用于治疗线粒体疾病的疗法。

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